Nolting Birte
Biotherapeutics Research and Development, Pfizer, Pearl River, NY, USA.
Methods Mol Biol. 2013;1045:71-100. doi: 10.1007/978-1-62703-541-5_5.
Antibody-drug conjugates (ADCs), which combine the specificity, favorable pharmacokinetics, and biodistribution of a monoclonal antibody (mAb) with the cytotoxic potency of a drug, are promising new therapies for cancer. Along with the development of monoclonal antibodies (mAbs) and cytotoxic drugs, the design of the linker is of essential importance, because it impacts the efficacy and tolerability of ADCs. The linker needs to provide sufficient stability during systemic circulation but allow for the rapid and efficient release of the cytotoxic drug in an active form inside the tumor cells. This review provides an overview of linker technologies currently used for ADCs and advances that have resulted in linkers with improved properties. Also provided is a brief summary of some considerations for the conjugation of antibody and drug linker such as drug-to-antibody ratio and site of conjugation.
抗体药物偶联物（ADCs）将单克隆抗体（mAb）的特异性、良好的药代动力学和生物分布与药物的细胞毒性相结合，是很有前景的癌症新疗法。随着单克隆抗体（mAbs）和细胞毒性药物的发展，连接子的设计至关重要，因为它会影响ADC的疗效和耐受性。连接子需要在全身循环过程中提供足够的稳定性，但要能使细胞毒性药物在肿瘤细胞内以活性形式快速有效地释放。本文综述了目前用于ADCs的连接子技术以及由此产生的具有改进特性的连接子的进展。还简要总结了抗体与药物连接子偶联时的一些注意事项，如药物与抗体的比例和偶联位点。
